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PubMed1985

Forskolin activation of serotonin-stimulated adenylate cyclase in the liver fluke Fasciola hepatica.

Properties of forskolin activation of adenylate cyclase in the liver fluke Fasciola hepatica are described. Forskolin stimulated adenylate cyclase activity in cell-free fluke particles to levels more than 30-fold above the basal rate. This activation was not dependent on guanine nucleotides and, upon washing of the particles, was rapidly reversed. Forskolin potentiated the activation of adenylate cyclase by serotonin (5-HT) and lysergic acid diethylamide (LSD), resulting in both an increase in the maximal level of enzyme activity and a decrease in the apparent activation constant (KA). The 5-HT antagonist 2-bromo-LSD did not inhibit enzyme activation by forskolin. Furthermore, forskolin had no effect on specific [3H]LSD binding to fluke particles. Activation of adenylate cyclase by sodium fluoride or guanine nucleotides was modified in a complex manner by forskolin with both stimulatory and inhibitory effects present. The results suggest that forskolin does not interact directly with the 5-HT receptor coupled to adenylate cyclase. Instead, it appears that forskolin effects are, at least in part, due to its ability to alter the interaction between the regulatory and catalytic components of adenylate cyclase. Incubation of intact flukes with forskolin increased their cAMP levels 2- to 3-fold. The concentration dependence of this response was similar to that for forskolin activation of adenylate cyclase in fluke particles, with 300 microM forskolin giving the maximum response. Forskolin and other agents that increased fluke cAMP levels also stimulated fluke motility.

Adenylyl Cyclases↗
PubMed1986

125I-LSD autoradiography confirms the preferential localization of caudate-putamen S2 receptors to the caudal (peripallidal) region.

The in vitro binding of 125I-lysergic acid diethylamide (LSD) to horizontal sections of rat brain was quantified with computer-assisted autoradiography. Specific binding of 125I-LSD to D2 and S2 sites, defined with 5 microM (+)-butaclamol, was 65-94% of the total binding. Identification of S2 sites with 50 nM ketanserin showed that over 90% of the butaclamol-displaced 125I-LSD binding in the frontal, cingulate and parietal neocortex was to S2 sites (22-55 fmol/mg protein). 125I-LSD also labeled a dense population of S2 sites (16 fmol/mg protein) in the caudal caudate-putamen at the level of the globus pallidus which exceeded by 5-fold the concentration of S2 sites (3 fmol/mg protein) in more rostral portions of the caudate-putamen. The peripallidal distribution of S2 sites was identical to that observed previously with the less selective S2 label, [3H]spiperone. The dense concentration of S2 sites in the caudal caudate-putamen and their overlap with D2 binding sites indicates that the peripallidal neostriatum may play an important role in interactions between dopamine and serotonin.

Animals↗
PubMed1996

Alterations in responses to LSD in humans associated with chronic administration of tricyclic antidepressants, monoamine oxidase inhibitors or lithium.

This study sought to investigate possible interactions between antidepressant agents and lysergic acid diethylamide (LSD) in humans through the use of retrospective questionnaires. Ten subjects were identified who used LSD during chronic (3 weeks or longer) periods of antidepressant administration. These subjects were asked to describe the phenomenological effects of self-administered hallucinogens prior to and during antidepressant treatment; a structured, standardized questionnaire was used to evaluate LSD experiences. Chronic tricyclic antidepressant administration was associated with subjective increases in physical, hallucinatory and psychological responses to LSD. Similarly, subjects receiving lithium chronically also reported increases in their responses to LSD. In contrast, subjects who had been chronically taking an monoamine oxidase (MAO) inhibitor reported subjective decreases in the effects of LSD. This is similar to a previous report by our group of a decreased response to LSD in individuals who were chronically taking serotonin-selective antidepressants. These altered responses to LSD most likely involve differential changes in central serotonin and dopamine receptor systems and are consistent with other recent data suggesting that the clinical efficacy of different classes of antidepressants may not necessarily rely on a common mechanism of action in the brain.

Adult↗
PubMed2003

Serotonergic/glutamatergic interactions: the effects of mGlu2/3 receptor ligands in rats trained with LSD and PCP as discriminative stimuli.

RATIONALE: On the basis of electrophysiological evidence, it has been proposed that both antagonism of NMDA receptors by drugs such as PCP and stimulation of 5- HT(2A) receptors by drugs such as LSD result in the release of glutamate. Furthermore, it has been observed that antagonists and agonists at mGlu(2/3) receptors increase and decrease, respectively, the release of glutamate. Taken together, these observations predict behaviorally significant interactions between ligands at mGlu(2/3) receptors and hallucinogens such as LSD and PCP. OBJECTIVE: The present study sought to test in rats the glutamate hypothesis of hallucinogenesis using drug-induced stimulus control as the dependent variable and selected glutamatergic and serotonergic receptor ligands as independent variables. METHODS: Male F-344 rats were trained in a two-lever, fixed ratio 10, food-reinforced task with either phencyclidine (PCP; 3.0 mg/kg; i.p.; 30 min pretreatment) or lysergic acid diethylamide (LSD; 0.1 mg/kg; IP; 15 min pretreatment) as discriminative stimuli. The interactions of PCP and the mGlu(2/3) selective ligands, LY341495 and LY379268, with stimulus control by LSD were determined. The effects of these drugs were compared with those of serotonergic antagonists known to antagonize the stimulus effects of LSD, specifically, pirenperone and M100907. RESULTS: Stimulus control by LSD was potentiated by both PCP and the mGlu(2/3) antagonist, LY341495. In tests of antagonism, stimulus control by LSD was significantly but incompletely diminished by the mGlu(2/3) agonist, LY379268; this result was in contrast with the complete antagonism of LSD by both pirenperone and M100907. In PCP-trained rats, LY341495 was without effect on stimulus control by an intermediate dose of PCP. In contrast, the training dose of PCP was significantly but incompletely antagonized by LY379268. CONCLUSIONS: These data, obtained using a stimulus control model of the hallucinogenic effects of PCP and LSD, provide support for the hypothesis that glutamate release is a factor in hallucinogenesis by both 5-HT(2) agonists and non-competitive NMDA antagonists.

Animals↗
PubMed1983

Modification of the pigment screening of the frog retina following administration of neuroactive drugs.

Pigment screening (PS) occurs in the retina of lower vertebrates and consists of the bidirectional migration (vitreally or sclerally) of melanin granules into processes of the pigment epithelium that extend between photoreceptors, in response to changes in the illumination conditions. We have studied the effect of some neuroactive drugs on the PS of frogs maintained under cyclic lighting conditions or dark-adapted. The drugs, administered intravenously were: lysergic acid diethylamide (LSD), mescaline, d-amphetamine, the LSD analogue lisuride and the LSD derivative 2-bromolysergic acid (BOL). All the drugs used--with the exception of mescaline--modify the bidirectional migration of the pigment induced by the two illumination conditions in a different way. This suggests that in general these substances interact in some way with those processes which normally produce the well-defined PS pattern. It has been possible to discriminate two opposite effects on the retinal PS induced by two chemically related substances (LSD and lisuride) only one of which (LSD) has potent hallucinogenic properties.

Animals↗
PubMed2003

Serotonin receptors in platelets of bipolar and schizoaffective patients: effect of lithium treatment.

RATIONALE: Abnormalities of serotonin (5HT) function have been implicated in mood disorders, and lithium treatment may produce its beneficial effects by modifying serotonergic mechanisms. It has also been observed that 5HT2A receptors are upregulated both in the postmortem brain and platelets of patients with depression and suicidal behavior. However, the role of 5HT2A receptors in bipolar disorders and in the mechanism of action of lithium is unclear. OBJECTIVE: The major objective of this study was to examine if abnormalities of 5HT2A receptors are associated with bipolar or schizoaffective disorders and if treatment with lithium would cause changes in the 5HT2A receptors. METHODS: 5HT2A receptors were studied in the platelets obtained from drug-free normal control subjects and patients with bipolar ( n=41) or schizoaffective ( n=20) disorders during a drug-free washout period and after treatment (4.0+/-0.44 weeks) with lithium ( n=16). The Bmax and K(D) of 5HT2A receptors were quantitated by binding techniques using [125I]lysergic acid diethylamide (LSD) as a ligand. RESULTS: We observed that the 5HT2A receptor Bmax was increased in platelets obtained from drug-free bipolar or schizoaffective patients as compared with normal control subjects. The 5HT2A receptor density was even more increased in bipolar or schizoaffective suicidal patients, and the 5HT2A receptor Bmax in the non-suicidal bipolar or schizoaffective subgroup also was significantly higher than in normal control subjects. Treatment with lithium caused a significant increase in the B(max) of platelet 5HT2A receptors in bipolar or schizoaffective patients. CONCLUSIONS: Our studies indicate that increased 5HT2A receptors may be associated with the pathophysiology of bipolar illness and that treatment with lithium further increases the density of 5HT2A receptors. Whether this increase in 5HT2A receptors caused by lithium is associated with its therapeutic mechanism of action is unclear. It is also not clear whether the increase in 5HT2A receptors in bipolar or schizoaffective patients, or in suicidal bipolar or schizoaffective patients, is a trait or state marker.

Adult↗
PubMed1988

Differences in the stimulus properties of 3,4-methylenedioxyamphetamine and 3,4- methylenedioxymethamphetamine in animals trained to discriminate hallucinogens from saline.

The stimulus properties of 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and several related compounds were compared to those of (+)-lysergic acid diethylamide (LSD) and mescaline (3,4,5-trimethoxyphenylethylamine) in a two-lever, water-reinforced, drug discrimination task. In animals trained to discriminate LSD (0.08 mg/kg) from saline (n = 8), LSD-like responding occurred during substitution (generalization) tests with sufficiently high doses of (+/- )-2,5-dimethoxy-4-methylamphetamine, LSD, mescaline, psilocybin and (-)-MDA; saline appropriate responding occurred after (+)-MDA and both (+)- and (+)- and (-)-MDMA. In animals trained to discriminate mescaline (10 mg/kg; n = 8), (-)-MDA, (+)-MDA, (-)-MDMA and (+)-MDMA as well as (+/- )-2,5-dimethoxy-4-methylamphetamine, LSD, mescaline and psilocybin mimicked the training drug. Neither (+)-amphetamine nor cocaine produced mescaline-like responding; fenfluramine substituted partially for mescaline but not LSD. Because all of the phenylisopropylamine enantiomers mimicked the potent hallucinogen mescaline (10 mg/kg), these results do not support suggestions that similarities in the behavioral effects of "designer" drugs such as MDA and MDMA to those of hallucinogens are limited to (-)-MDA. They also indicate that, although LSD and mescaline may be pharmacologically similar (in other assays), these compounds do not have identical stimulus properties.

3,4-Methylenedioxyamphetamine↗
PubMed1985

The effects of LSD in the guinea-pig ileum. Inhibition of acetylcholine release and stimulation of smooth muscle.

The effects of lysergic acid diethylamide (LSD) on acetylcholine release and on smooth muscle tone were studied in the myenteric plexus-longitudinal muscle preparation of the guinea pig. LSD (0.01-10 microM) depressed in a concentration-dependent manner the electrically-evoked [3H]-acetylcholine outflow from strips preincubated with [3H]-choline. The maximal effect was a 45% inhibition by 1 microM LSD. The spontaneous outflow was not affected. Metitepine competitively antagonized (pA2 8.0) the LSD-induced reduction of the evoked outflow. Tolazoline and mepyramine did not affect the inhibitory action of LSD. The contractions in response to electrical stimulation were enhanced by 34% in the presence of 0.1 microM LSD. Other concentrations of LSD did not affect the twitches. LSD caused an increase in muscle tone which was antagonized non-competitively by mepyramine, metitepine and ketanserin. Ketanserin was a competitive antagonist against the histamine-induced contractions of the longitudinal muscle (pA2 8.49). The results suggest that LSD stimulates presynaptically located 5-HT receptors and thereby decreases the evoked acetylcholine release. In addition, LSD increases smooth muscle tone either directly through stimulation of H1 receptors or indirectly via histamine release.

Acetylcholine↗
PubMed1993

Effects of agonists, partial agonists, and antagonists on the regulation of 5-hydroxytryptamine2 receptors in P11 cells.

Studies of the regulation of 5-hydroxytryptamine (5-HT2) receptors in vivo have generated anomalous and sometimes contradictory results. In particular, administration of antagonists unexpectedly results in a reduction in the density of 5-HT2 receptors. P11 cells, which express a high density of 5-HT2 receptors coupled to phosphoinositide hydrolysis, were used to investigate the regulation of receptors in vitro by agonists, partial agonists, and antagonists. (+/-)-2,5-Dimethoxy-4-iodophenylisopropylamine (DOI) and (+)-lysergic acid diethylamide (LSD) caused marked reductions in the density of 5-HT2 receptors as has been observed in vivo. Down-regulation was prevented by coincubation with ketanserin. The decrease in the density of 5-HT2 receptors after exposure to 5-HT, LSD, or DOI was time dependent and was not a consequence of residual drug in binding assays or irreversibly bound drug. The ability of 5-HT, DOI, and LSD to down-regulate 5-HT2 receptors was not proportional to the ability of these compounds to stimulate phosphoinositide hydrolysis. Ketanserin and mianserin, antagonists which cause paradoxical decreases in the density of 5-HT2 receptors in vivo, did not alter the density of 5-HT2 receptors on P11 cells, even after prolonged incubation with drug. Results of the current studies, which demonstrate agonist- but not antagonist-induced down-regulation of 5-HT2 receptors, lead to the conclusion that the ability of ketanserin and mianserin to down-regulate receptors in vivo is the result of indirect actions of these drugs and is unlikely to be a direct consequence of receptor occupancy by antagonists.

Amphetamines↗
PubMed1981

Inhibition of neurotransmitter receptor binding by ergot derivatives.

Bromocriptine, lergotrile, lisuride, metergoline, and the Sandoz ergot derivatives 25-397, 29-712, and 29-717 have been tested for their ability to inhibit the synaptic receptor binding of spiroperidol, 5-hydroxytryptamine (5-HT), d-lysergic acid diethylamide (LSD), quinuclidinyl benzilate (QNB), WB.4101, and gamma-aminobutyric acid (GABA). Only GABA binding was not affected, and QNB binding was decreased only by lergotrile and metergoline at high concentrations. The most potent inhibitors of the other ligands were bromocriptine and lisuride for spiroperidol (1-2 nMM), metergoline for 5-HT (29 nM), lisuride for LSD (15 nM), and lergotrile for WB.4101 (17 nM). The direct receptor effects of the ergot derivatives in vitro may contribute to understanding their in vivo effects on behavior and in predicting their therapeutic potential in neurological and neuroendocrine disorders.

Adrenergic alpha-Antagonists↗
PubMed1994

Autoradiographic comparison of [125I]LSD-labeled 5-HT2A receptor distribution in rat and guinea pig brain.

Although the density and distribution of 5-HT2A (5-hydroxytryptamine-2A) receptors is well established for rat brain, the 5-HT2A receptor distribution and density in guinea pig brain has not been extensively studied. In the present in vitro study, we have utilized 125I-lysergic acid diethylamide ([125I]LSD) to quantify and compare 5-HT2A receptor density in coronal sections of rat and guinea pig brain. Spiperone (1 microM) and sulpiride (1 microM) were used to displace [125I]LSD binding from 5-HT2A and D2 binding sites, respectively. Ligand binding was quantified by computer-aided image analysis densitometry (MCID). Similar to the rat, areas of highest specific 5-HT2A receptor binding (fmol/mg protein) in guinea pig brain included the claustrum and Layer 4 of the cerebral cortex. Significant binding was also found in remaining neocortical layers, islands of Calleja, caudate putamen, olfactory bulb, nucleus accumbens, and choroid plexus. While the rat brain exhibited a high level of specific binding in the tenia tecta and mammillary nuclei, little binding was observed in these regions in the guinea pig. In both rat and guinea pig, low specific binding was found in amygdaloid, thalamic, or cerebellar areas. These studies indicate a general similarity between 5-HT2A binding site distribution and relative density in guinea pig and rat brain but point to a few brain regions where significant differences exist.

Animals↗
PubMed1973

The 5-hydroxytryptamine-like actions of 5,6-dihydroxytryptamine.

1. With isolated preparations of rat stomach fundus as well as of duodenum and ileum of rats and guinea-pigs, 5,6-dihydroxytryptamine and 5,6-diacetoxytryptamine caused a contraction which was antagonized by methysergide and lysergic acid diethylamide (LSD), but not by atropine. Pretreatment of the animals with reserpine did not decrease the effect of the two indoleamines on the isolated ileum and duodenum.2. In anaesthetized guinea-pigs, 5,6-dihydroxytryptamine and its diacetyl derivative caused bronchoconstriction which was antagonized by methysergide, but not modified by pretreating the animals with reserpine.3. In anaesthetized cats, 5,6-dihydroxytryptamine had, in general, a hypotensive effect which was reversed by hexamethonium.4. 5,6-Dihydroxytryptamine also caused aggregation of isolated rabbit and human platelets and inhibited the platelet aggregation induced by 5-hydroxytryptamine (5-HT) plus adrenaline.5. The pattern of action of 5,6-hydroxytryptamine and 5,6-diacetoxytryptamine was qualitatively the same as that of 5-HT, but the potency of the compounds decreased in the order 5-HT, 5,6-dihydroxytryptamine, 5,6-diacetoxytryptamine both in vitro and in vivo.6. It is concluded that 5,6-dihydroxytryptamine and its diacetyl derivative stimulate postsynaptic 5-HT receptors, but that their effect is weaker than that of 5-HT.

Airway Resistance↗
PubMed1979

LSD-induced alterations of investigatory responding in rats.

The effects of lysergic acid diethylamide (LSD) on investigatory responses of rats in a novel hole-board were assessed in a series of experiments. LSD (40-160 micrograms/kg) altered the temporal distribution of "nose-poke" response during a 24-min session; LSD-treated rats responded less than controls initially, yet increased their response rates late in the session. This dose-dependent effect was not related to the time course of the drug's action nor to alterations in general locomotor activity. Only partial tolerance was found after eight daily injections of 100 micrograms/kg LSD. When handling stress was minimized by placing the animals in an anteroom for 10 min before starting the test, the distribution of responding was normal although the overall frequency was still reduced. Conversely, vigorous handling potentiated the LSD effect. These results are interpreted as indicating an increased sensitivity of the LSD-treated rats to the stimuli associated with being handled and placed into the novel hole-board rather than a direct effect on investigatory tendencies. This LSD-induced potentiation of defensive responses appears to compete with the active exploration of the novel environment.

Animals↗
PubMed1989

Electrophysiological assessment of putative antagonists of 5-hydroxytryptamine receptors: a single-cell study in the rat dorsal raphe nucleus.

The intravenous administration of low doses of lysergic acid diethylamide (LSD) or of the selective 5-hydroxytryptamine1A (5-HT1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) depresses the firing activity of dorsal raphe 5-HT-containing neurons, presumably via the activation of 5-HT1A receptors. The present studies were undertaken to determine the effect of different types of 5-HT receptor antagonists on this effect of LSD and 8-OH-DPAT. (-)-Propranolol (2 mg/kg i.v.), methiothepin (2 mg/kg i.p., twice daily for 4 days followed by an additional dose of 2 mg/kg i.p., prior to the experiment), pelanserine (0.5 mg/kg i.v.), and indorenate (125 micrograms/kg i.v.) failed to block the effects of either LSD or 8-OH-DPAT on the firing activity of 5-HT neurons of the dorsal raphe nucleus. However, spiperone (1 mg/kg i.v.) significantly reduced the effect of both LSD and 8-OH-DPAT. These results indicate that, among the five putative 5-HT receptor antagonists tested, only spiperone can antagonize the suppressant effect of 5-HT receptor agonists on the firing of dorsal raphe 5-HT neurons.

5-Methoxytryptamine↗
PubMed2004

The development of the medullary serotonergic system in the piglet.

The anatomy of the 5-HT system in the medulla oblongata is well defined in several vertebrate species, but not in the piglet. A detailed map and developmental profile of this system is particularly important in the piglet because this species increasingly is used as a model for physiological studies of medullary homeostatic control and its disorders in human infancy, especially the sudden infant death syndrome. Tryptophan hydroxylase immunohistochemistry was used to identify 5-HT cells and map their distribution in the medullae of piglets between postnatal days 4 and 30, the putative comparable period to early human infancy. Tritiated (3H)-lysergic acid diethylamide (LSD) binding to 5-HT1A-D and 5-HT2 receptors and 3H-8-hydroxy-2-[di-N-propylamine]tetralin (8-OH-DPAT) binding to 5-HT1A receptors were used to quantify and map the distribution of these serotonin receptors between 4 and 60 postnatal days. The distribution of 5-HT cells was similar to that observed in other vertebrate species, with cell bodies in and lateral to the caudal raphé. Tritiated-LSD and 3H-8-OH-DPAT binding both showed significant age-related changes in select raphé and extra-raphé subnuclei. Taken together, these findings suggest that while the medullary 5-HT cells are topographically in place at birth in the piglet, changes in 5-HT neurotransmission take place during the first 30 days of life, as reflected by changes in patterns of receptor binding. Therefore, the first 30 days of life represent a critical period in the development of the 5-HT system and the homeostatic functions it mediates.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1998

Determination of lysergide (LSD) and phencyclidine in biosamples.

Lysergic acid diethylamide (LSD) is difficult to detect and to quantify in biosamples because of its very low active dose. Although there are a number of tests available, routine analysis of LSD is rarely performed. Immunoassays largely vary in their specificity and cross-reactivities with other molecules often make these tests unreliable. Because of its low concentration and the instability of the derivatives (e.g. trimethylsilyl-LSD), routine gas chromatography-mass spectrometry (GC-MS) detection and quantitation of LSD remains a difficult task. The most promising procedures for LSD determination seems to be liquid chromatography-MS analysis using electrospray ionisation and selected ion monitoring (SIM). Extraction, derivatization, GC or high-performance liquid chromatography conditions and the different detection modes will be summarised. Phencyclidine (PCP) is an abused drug seldom found outside the United States. Well established detection and quantitation procedures include radioisotopic and nonradioisotopic immunoassays and GC-MS analysis using SIM mode with deuterated PCP as internal standard. Alternatively, GC with nitrogen-phosphorus detection or capillary electrophoresis has been used. Recent progress in PCP analysis will be summarised.

Chromatography, High Pressure Liquid↗
PubMed1996

The analysis of lysergide (LSD): the development of novel enzyme immunoassay and immunoaffinity extraction procedures together with an HPLC-MS confirmation procedure.

A forensic procedure for the screening and confirmation of the presence of lysergide (lysergic acid diethylamide, LSD) in urine is described together with the evaluation of a novel enzyme immunoassay (EIA) and immunoaffinity extraction procedure. Following initial screening using either an established radioimmunoassay (RIA) or a novel EIA procedure, a quantitative estimate is established using a conventional high performance liquid chromatography-fluorescence (HPLC) technique following solid phase extraction. Final confirmation and quantitation, without derivatization, is established using HPLC in combination with electrospray ionization (ESI) mass spectrometry using methysergide as an internal standard. The detection limit of LSD in urine is 0.5 ng/mL. A blind trial confirmed the validity of the results. The choice of internal standard is discussed. Consideration is given to the photosensitivity of LSD solutions. A study of potential interferants in the HPLC-MS confirmation of LSD is presented and shows that for the wide range of compounds studied, there are none that would interfere with this confirmation technique. A comparison is shown between solid phase and immunoaffinity extraction/clean up procedures, and between RIA and EIA screening procedures.

Chromatography, Affinity↗
PubMed1981

Multiple serotonin receptors: regional distribution and effect of Raphe lesions.

These studies confirm and extend the recent work suggesting that [3H]lysergic acid diethylamide (LSD) labels two distinct binding sites in rat brain resembling serotonin (5HT) receptors. Although Scatchard analyses of [3H]LSD binding to membranes prepared from cortex/hippocampus were linear, the heterogeneity of the [3H]LSD binding sites was clearly demonstrated in displacement studies. The displacement curves for both 5HT and spiperone were bisigmoidal with the concentration required to saturate the high affinity components nearly 3 orders of magnitude lower than the concentration necessary to saturate the low affinity components. Additivity studies suggested that the sites with high affinity for 5HT and spiperone are different, independent sites. These sites are referred to as 5HT, and 5HT2, respectively. Regional analyses showed, that in the frontal cortex, the density of the 5HT2 site was slightly greater than the 5HT1 site, whereas the 5HT1 site was predominant in all other brain areas, including the spinal cord. The pharmacological properties of the two sites have features in common with 5HT receptors; however, electrolytic lesions of the midbrain raphe nuclei did not change the densities or binding constants of the two apparent 5HT receptor subtypes, even though the number of high affinity 5HT uptake sites was markedly reduced.

Animals↗